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1.
J Appl Toxicol ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39147402

RESUMO

The potential harms and benefits of e-cigarettes, or electronic nicotine delivery systems (ENDS), have received significant attention from public health and regulatory communities. Such products may provide a reduced risk means of nicotine delivery for combustible cigarette smokers while being inappropriately appealing to nicotine naive youth. Numerous authors have examined the chemical complexity of aerosols from various open- and closed-system ENDS. This body of literature is reviewed here, with the risks of ENDS aerosol exposure among users evaluated with a margin of exposure (MoE) approach for two non-carcinogens (methylglyoxal, butyraldehyde) and a cancer risk analysis for the carcinogen N-nitrosonornicotine (NNN). We identified 96 relevant papers, including 17, 13, and 5 reporting data for methylglyoxal, butyraldehyde, and NNN, respectively. Using low-end (minimum aerosol concentration, low ENDS use) and high-end (maximum aerosol concentration, high ENDS use) assumptions, estimated doses for methylglyoxal (1.78 × 10-3-135 µg/kg-bw/day) and butyraldehyde (1.9 × 10-4-66.54 µg/kg-bw/day) corresponded to MoEs of 227-17,200,000 and 271-280,000,000, respectively, using identified points of departure (PoDs). Doses of 9.90 × 10-6-1.99 × 10-4 µg/kg-bw/day NNN corresponded to 1.4-28 surplus cancers per 100,000 ENDS users, relative to a NNN-attributable surplus of 7440 per 100,000 cigarette smokers. It was concluded that methylglyoxal and butyraldehyde in ENDS aerosols, while not innocuous, did not present a significant risk of irritant effects among ENDS users. The carcinogenic risks of NNN in ENDS aerosols were reduced, but not eliminated, relative to concentrations reported in combustible cigarette smoke.

2.
Malays J Med Sci ; 31(2): 130-141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694573

RESUMO

Background: The objective of this study is to assess the risk of exposure of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) in meat and fish-based products marketed in Malaysia using the margin of exposure (MOE) approach. Methods: Benchmark Dose (BMD) software was used to model the BMD at a lower end of a one-sided 95% confidence interval with a 10% incremental risk (BMDL10) of PAHs and HCAs from different target organ toxicities. The MOEs of PAHs and HCAs in meat and fish-based products were determined by utilising the calculated BMDL10 values and estimated daily intake of meat and fish-based products from published data. Results: The calculated BMDL10 values of PAHs (i.e. benzo[a]pyrene [BaP] and fluoranthene [FA]) and HCAs (i.e. 2-amino-3,8,dimethylimidazo[4,5-f]quinoxaline [MeIQx] and 2-amino-1-methyl-6-phenylimidazo[4,5,6]pyridine [PhIP]) ranged from 19 mg/kg bw/day to 71,801 mg/kg bw/day. The MOE of BaP ranged from 41,895 to 71,801 and that of FA ranged from 19 to 1412. As for MeIQx and PhIP, their MOEs ranged from 6,322 to 7,652 and from 2,362 to 14,390, respectively. Conclusion: The MOEs of FA, MeIQx and PhIP were lower than 10,000, indicating a high concern for human health and therefore demanding effective risk management actions.

3.
Environ Sci Technol ; 57(21): 7978-7988, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37162498

RESUMO

The inhalation exposure of pesticide applicators and residents who live close to pesticide-treated fields is a worldwide concern in public health. Quantitative assessment of exposure to pesticide inhalation health risk highlights the need to accurately assess the bioaccessibility rather than the total content in ambient air. Herein, we developed an in vitro method to estimate the inhalation bioaccessibility of emamectin benzoate and validated its applicability using a rat plasma pharmacokinetic bioassay. Emamectin benzoate was extracted using the Gamble solution, with an optimized solid-to-liquid ratio (1/250), extraction time (24 h), and agitation (200 rpm), which obtained in vitro inhalation bioaccessibility consistent with its inhalation bioavailability in vivo (32.33%). The margin of exposure (MOE) was used to assess inhalation exposure risk. The inhalation unit exposures to emamectin benzoate of applicators and residents were 11.05-28.04 and 0.02-0.04 ng/m3, respectively, varying markedly according to the methods of application, e.g., formulations and nozzles. The inhalation risk assessment using present application methods appeared to be acceptable; however, the MOE of emamectin benzoate might be overestimated by 32% without considering inhalation bioaccessibility. Collectively, our findings contribute insights into the assessment of pesticide inhalation exposure based on bioaccessibility and provide guidance for the safe application of pesticides.


Assuntos
Resíduos de Praguicidas , Praguicidas , Animais , Ratos , Exposição por Inalação , Ivermectina/análise , Resíduos de Praguicidas/análise
4.
Arch Toxicol ; 97(4): 1069-1077, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36800005

RESUMO

While trifluoroacetic acid has limited technical uses, the highly water-soluble trifluoroacetate (TFA) is reported to be present in water bodies at low concentrations. Most of the TFA in the environment is discussed to arise from natural processes, but also with the contribution from decomposition of environmental chemicals. The presence of TFA may result in human exposures. For hazard and risk assessment, the mammalian toxicity of TFA and human exposures are reviewed to assess the margin of exposures (MoE). The potential of TFA to induce acute toxicity is very low and oral repeated dose studies in rats have identified the liver as the target organ with mild liver hypertrophy as the lead effect. Biomarker analyses indicate that TFA is a weak peroxisome proliferator in rats. TFA administered to rats did not induce adverse effects in an extended one-generation study and in a developmental toxicity study or induce genotoxic responses. Based on recent levels of TFA in water and diet, MoEs for human exposures to TFA are well above 100 and do not indicate health risks.


Assuntos
Exposição Ambiental , Poluentes Químicos da Água , Humanos , Animais , Ratos , Ácido Trifluoracético/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Fígado , Água , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Mamíferos
5.
Arch Toxicol ; 97(9): 2303-2328, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37402810

RESUMO

Genotoxicity data are mainly interpreted in a qualitative way, which typically results in a binary classification of chemical entities. For more than a decade, there has been a discussion about the need for a paradigm shift in this regard. Here, we review current opportunities, challenges and perspectives for a more quantitative approach to genotoxicity assessment. Currently discussed opportunities mainly include the determination of a reference point (e.g., a benchmark dose) from genetic toxicity dose-response data, followed by calculation of a margin of exposure (MOE) or derivation of a health-based guidance value (HBGV). In addition to new opportunities, major challenges emerge with the quantitative interpretation of genotoxicity data. These are mainly rooted in the limited capability of standard in vivo genotoxicity testing methods to detect different types of genetic damage in multiple target tissues and the unknown quantitative relationships between measurable genotoxic effects and the probability of experiencing an adverse health outcome. In addition, with respect to DNA-reactive mutagens, the question arises whether the widely accepted assumption of a non-threshold dose-response relationship is at all compatible with the derivation of a HBGV. Therefore, at present, any quantitative genotoxicity assessment approach remains to be evaluated case-by-case. The quantitative interpretation of in vivo genotoxicity data for prioritization purposes, e.g., in connection with the MOE approach, could be seen as a promising opportunity for routine application. However, additional research is needed to assess whether it is possible to define a genotoxicity-derived MOE that can be considered indicative of a low level of concern. To further advance quantitative genotoxicity assessment, priority should be given to the development of new experimental methods to provide a deeper mechanistic understanding and a more comprehensive basis for the analysis of dose-response relationships.


Assuntos
Dano ao DNA , Mutagênicos , Mutagênicos/toxicidade , Mutagênicos/análise , DNA , Medição de Risco , Testes de Mutagenicidade/métodos
6.
Regul Toxicol Pharmacol ; 145: 105519, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866701

RESUMO

Formaldehyde has been classified as carcinogenic to humans by International Agency for Research on Cancer and found in personal care (PC) products containing formaldehyde-donor (FD) preservatives. However, the cancer risk associated with the use of FD-containing PC products has not been well established. Our study provides the quantitative cancer risk assessment of formaldehyde in FD-containing PC products. The carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy was used in this risk assessment to provide reliable exposure information to formaldehyde in PC products and aqueous solutions containing sodium hydroxymethylglycinate. The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMDs) for 10% effect. For hemolymphoreticular neoplasias in male rats, a BMD of 28.03 mg/kg/day and a BMD lower confidence limit (BMDL) of 2.52 mg/kg/day were calculated from available long-term animal experiments. The worst-case consumer exposure to formaldehyde from FD-containing PC products was 0.007 µg/kg/day. Comparing the consumer exposure with BMDL, the resulting MOE was 360,000 for the worst-case scenario. The consumer exposure to formaldehyde (0.007 µg/kg/day) from using FD-containing PC products represents less than 1.0 × 10-6 % of background level endogenous formaldehyde (878-1310 mg/kg/day). The cancer risk from formaldehyde to consumers using FD-containing PC products is negligible.


Assuntos
Cosméticos , Neoplasias , Humanos , Masculino , Ratos , Animais , Cosméticos/toxicidade , Cosméticos/química , Formaldeído/toxicidade , Conservantes Farmacêuticos , Carcinógenos , Medição de Risco
7.
Subst Use Misuse ; 58(3): 346-353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36630411

RESUMO

BACKGROUND: Smoking is the largest preventable cause of death in the world with around eight million estimated premature deaths per year. In response to the harmful effects of conventional tobacco products the tobacco industry has launched a new type of products called Heated tobacco products (HTP) and e-cigarettes, which are considered safer for human health than conventional cigarettes. MATERIALS AND METHODS: The research was conducted by searching the scientific literature using platforms "Google scholar," "PubMed" and "Science Direct." To compare the non-carcinogenic and carcinogenic risk of HTP products and conventional cigarettes, margin of exposure and lifetime excess cancer risk were calculated using data obtained from a scientific literature search.HTP products have shown a reduced risk to human health compared to the conventional cigarettes, although they still contain compounds that can be dangerous to human health. There is not enough data obtained from independent studies that could safely indicate that these reduced amounts of toxic chemical entities in the composition of HTP do not induce any harmful effect. CONCLUSION: Further research is needed to determine the harmful effects of HTP aerosol, as well as to tighten the legislation that would limit the production, import and distribution of these products worldwide until their safety for human health is confirmed with a sufficient number of transparent and representative results obtained in independent scientific studies.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Fumar , Nicotiana/química , Fumar Tabaco
8.
Environ Geochem Health ; 45(6): 3789-3804, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36580188

RESUMO

Chlorinated paraffins (CPs) are ubiquitous anthropogenic contaminants that have been found in various environmental media. The objective of this study was to determine concentrations, spatial distribution, possible sources and potential health risk of SCCPs and MCCPs in urban road dust collected from Shanghai, China. The concentrations ranged from 9.74 to 11,400 ng g-1 for ΣSCCPs, 44.1 to 49,900 ng g-1 for ΣMCCPs and 53.9 to 61,400 ng g-1 for total CPs, respectively. MCCPs were the dominant component in all road dust, averagely accounting for 82.8% of total CPs. The concentrations of CPs in dust collected from traffic and commercial areas were significantly higher than those from campus, industrial, park and residential areas (p < 0.01), which could be attributed to tire wear in heavy traffic. All dust samples were divided into two groups by hierarchical cluster analysis for both SCCPs and MCCPs, and the most abundant homologue groups in most samples were C10Cl7-10 and C13Cl7-9 for SCCPs, and C14Cl7-9 and C15Cl8-9 for MCCPs. Correlation analysis showed that all carbon homologues in road dusts were highly correlated each other, suggesting SCCPs and MCCPs in dust maybe came from similar sources. Three sources for CPs in dust samples were apportioned by the PMF model; their relative contributions to the total CPs burden in dust were 25.6% for factor 1 (commercial CP mixture), 13.7% for factor 2 (long-distance transport) and 60.7% for factor 3 (commercial CP mixture). The median estimated daily intakes of total CPs via road dust were 1.78 × 10-5 for children and 3.0 × 10-6 mg kg-1 day-1 for adults, respectively. Quantitative risk assessment using non-cancer hazard index and total margin of exposure of total CPs indicated that total CPs at the present level in road dust pose no significant risk for both children and adults in Shanghai.


Assuntos
Poeira , Hidrocarbonetos Clorados , Adulto , Criança , Humanos , China , Poeira/análise , Parafina/análise , Monitoramento Ambiental , Hidrocarbonetos Clorados/análise
9.
Wei Sheng Yan Jiu ; 52(4): 611-617, 2023 Jul.
Artigo em Zh | MEDLINE | ID: mdl-37679079

RESUMO

OBJECTIVE: To investigate lead contamination in commercial foods in Chongqing City, and to assess the health risk of dietary lead exposure of residents in Chongqing City. METHODS: Lead concentration data was obtained from the food safety risk monitoring system, which included a total of 2347 lead-containing food samples in 11 categories in Chongqing from 2016 to 2020. Consumption data was derived from the China Health and Nutrition Survey Project in Chongqing in 2018(3 day, 24 h dietary recall survey). The dietary exposure to lead of residents in Chongqing was calculated by the Monte Carlo simulation method and the margin of exposure(MOE) method was used to evaluate the health risk of the population. RESULTS: The average content of lead in 2347 food samples from 11 categories ranged from 0.0328 to 0.0363 mg/kg, with an overall detection rate of 58.5%. For people aged between 3-6, 7-17, 18-59, and ≥ 60 years, the mean dietary lead intakes in Chongqing were 0.935-1.070, 0.600-0.684, 0.367-0.416, 0.369-0.419 µg/(kg·BW·d), respectively; and the high levels of dietary lead exposure(P95) were 1.642-1.852, 1.147-1.299, 0.651-0.729, 0.659-0.740 µg/(kg·BW·d), respectively. MOE values for lead were less than 1 for age groups 3-6 and 7-17 years. Mean MOE values for lead were greater than 1 for ages 18 to 59 and ≥ 60. Cereals and their products, vegetables and their products, and meat and meat products were the main sources of dietary lead exposure, accounting for more than 85% of the total dietary lead exposure. CONCLUSION: There are potential health risks of lead for residents in Chongqing.


Assuntos
Exposição Dietética , Chumbo , Humanos , Pré-Escolar , Exposição Dietética/efeitos adversos , China , Grão Comestível , Medição de Risco
10.
Zhongguo Zhong Yao Za Zhi ; 48(6): 1491-1497, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-37005836

RESUMO

By investigating the contamination status and predicting the exposure risk of mycotoxin in Coicis Semen, we aim to provide guidance for the safety supervision of Chinese medicinal materials and the formulation(revision) of mycotoxin limit standards. The content of 14 mycotoxins in the 100 Coicis Semen samples collected from five major markets of Chinese medicinal materials in China was determined by UPLC-MS/MS. The probability evaluation model based on Monte Carlo simulation method was established after Chi-square test and One-way ANOVA of the sample contamination data. Health risk assessment was performed on the basis of margin of exposure(MOE) and margin of safety(MOS). The results showed that zearalenone(ZEN), aflatoxin B_1(AFB_1), deoxynivalenol(DON), sterigmatocystin(ST), and aflatoxin B_2(AFB_2) in the Coicis Semen samples had the detection rates of 84%, 75%, 36%, 19%, and 18%, and the mean contamination levels of 117.42, 4.78, 61.16, 6.61, and 2.13 µg·kg~(-1), respectively. According to the limit standards in the Chinese Pharmacopoeia(2020 edition), AFB_1, AFs and ZEN exceeded the standards to certain extents, with the over-standard rates of 12.0%, 9.0%, and 6.0%, respectively. The exposure risks of Coicis Semen to AFB_1, AFB2, ST, DON, and ZEN were low, while 86% of the samples were contaminated with two or more toxins, which needs more attention. It is suggested that the research on the combined toxicity of different mycotoxins should be strengthened to accelerate the cumulative exposure assessment of mixed contaminations and the formulation(revision) of toxin limit standards.


Assuntos
Coix , Micotoxinas , Humanos , Micotoxinas/análise , Aflatoxina B1/análise , Cromatografia Líquida/métodos , Contaminação de Alimentos/análise , Espectrometria de Massas em Tandem/métodos
11.
J Appl Toxicol ; 42(12): 1873-1889, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35199353

RESUMO

2-Amino-2-methyl-1-propanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCPs); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in-depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP-containing PCPs were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP-choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low-density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of PCPs is highly unlikely to result in toxicologically significant systemic concentrations of AMP and thus hepatotoxicity. We concluded that dermal exposure to AMP in PCPs is not anticipated to result in an increased risk of hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fígado Gorduroso , Humanos , Animais , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Colina , Monofosfato de Adenosina
12.
J Environ Manage ; 309: 114697, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35151136

RESUMO

One of the challenges while assessing the aggregate exposure risk of pesticides is quantifying exposure doses from various exposure pathways. To address this issue, a regulatory screening approach is proposed for evaluating pesticide allocation factors (AFs) for major exposure pathways for rural and urban residents. This was achieved by integrating dynamiCrop and other screening models to estimate the potential human intake of residues from major crops at harvest, livestock products, and main environmental media (air, water, and soil). The AFs were calculated from the average daily dose factors (ADDFs) of pesticides via major exposure pathways, where a large AF of an exposure pathway indicates that a greater margin of exposure should be given to that exposure pathway. The simulated results for many current-use pesticides showed that the ingestion of crops had pesticide AFs close to 1.0, which indicated that the crop exposure pathway contributed to a significant portion of the total exposure to pesticides. In contrast, for legacy pesticides with high lipophilicity and low degradability in the environment, the simulated AFs for major environmental compartments (air, freshwater, and soil) accounted for relatively large exposures. As legacy pesticides have been banned globally, exposure pathways via the food web and environmental media cannot be neglected because of their high lipophilicity and environmental persistence. Although other factors such as geographical conditions and living habits should be considered to improve the spatial resolution of the model, the method proposed in this study can serve as a preliminary tool to conduct screening-level risk assessments for populations by considering the allocated exposure to pesticides via major exposure pathways.


Assuntos
Praguicidas , Produtos Agrícolas , Exposição Ambiental/análise , Humanos , Praguicidas/análise , Medição de Risco , Solo
13.
Arch Toxicol ; 95(1): 283-298, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33025067

RESUMO

Health risk associated with the use of combustible cigarettes is well characterized and numerous epidemiological studies have been published for many years. Since more than a decade, innovative non-combusted tobacco products have emerged like heated tobacco products (HTP) or electronic cigarettes (EC). Long-term effects of these new products on health remain, however, unknown and there is a need to characterize associated potential health risks. The time dedicated to epidemiological data generation (at least 20 to 40 years for cancer endpoint), though, is not compatible with innovative development. Surrogates need, therefore, to be developed. In this work, non-cancer and cancer risks were estimated in a range of HTP and commercial combustible cigarettes based upon their harmful and potentially harmful constituent yields in aerosols and smoke, respectively. It appears that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and commercial cigarettes, and significantly higher margin of exposure for non-cancer risk was observed for HTPs when compared to commercial cigarettes. The same approach was applied to two commercial ECs. Similar results were also found for this category of products. Despite uncertainties related to the factors used for the calculations and methodological limitations, this approach is valuable to estimate health risks associated to the use of innovative products. Moreover, it acts as predictive tool in absence of long-term epidemiological data. Furthermore, both cancer and non-cancer risks estimated for HTPs and ECs highlight the potential of reduced risk for non-combusted products when compared to cigarette smoking.


Assuntos
Fumar Cigarros/efeitos adversos , Vapor do Cigarro Eletrônico/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias/epidemiologia , Produtos do Tabaco/efeitos adversos , Vaping/efeitos adversos , Aerossóis , Humanos , Exposição por Inalação , Neoplasias/diagnóstico , Medição de Risco , Fatores de Risco
14.
Inhal Toxicol ; 33(3): 81-95, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33876709

RESUMO

BACKGROUND: Risk assessment of individual tobacco smoke components is important for the purpose of prioritization or selecting chemicals for monitoring products. Smoking is characterized by a highly varying, intermittent exposure and the challenge is to choose the most appropriate dose metric. METHODS: Generally, average daily exposure estimates are used as dose metric, without considering temporal determinants. The applicability hereof is discussed in the context of choosing dose metrics for local respiratory tract effects and for systemic effects in a smoking scenario or for the use of e-cigarettes. RESULTS: Using average daily exposure estimates for the smoking scenario can lead to erroneous risk evaluations for several reasons. Inhaled peak air concentrations during a puff can be two to three orders of magnitude higher than the calculated average daily inhaled concentration, which may impact the assessment of both systemic and local health effects. A pragmatic risk assessment is proposed, based on the Margin of Exposure (MoE) approach. The choice of an appropriate dose metric, such as inhaled concentration, inhaled dose or absorbed dose, depends on the type of effect. Temporal characteristics should be considered in the final step of the MoE approach, as is illustrated by two cases, glycerol and benzene. CONCLUSION: The choice of an appropriate dose metric and inclusion of temporal determinants are important aspects in the risk assessment of individual smoke components. The proposed MoE approach provides the opportunity to weigh smoking-related exposure characteristics during the final step of the risk evaluation.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotiana/química , Medição de Risco/métodos , Fumaça/análise , Aerossóis/efeitos adversos , Aerossóis/química , Humanos , Fumaça/efeitos adversos , Nicotiana/efeitos adversos
15.
Inhal Toxicol ; 33(4): 128-142, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33957849

RESUMO

OBJECTIVE: The objective of this study was the assessment of risks from inhalation exposure of Austrian smokers to cadmium through established toxicological approaches with emphasis on the exposure assessment component, which is challenging regarding the actual amount of metal that is inhaled and the simulation of the smoking pattern. MATERIALS AND METHODS: Exposure assessment comprised an estimation of the proportion of cadmium inhaled through smoking and actual occurrence data in tobacco products and survey smoking habits, which were integrated in alternative scenarios through a deterministic and a probabilistic Monte Carlo simulation method. Risks were characterized through the comparison of the exposure with health-based guidance values, as well as through the assessment of the excess lifetime cancer risk (ELCR), the non-cancer hazard quotient (NCHQ), and the margin of exposure (MOE). The strengths, the uncertainties, and the limitations of the different methodologies were discussed. RESULTS AND DISCUSSION: Upper exposures are close or exceed the Permitted Daily Exposure. Respiratory ELCRs are unacceptable compared to the benchmark range of 1.0E-06 to 1.0E-04. Renal and respiratory NCHQs exceed the target value of 1.0 by 3- to 17-fold. MOEs are not protective enough for cancer and non-cancer effects. The amount of cadmium that reaches the lung is a key source of uncertainty. CONCLUSION: Probabilistic estimates provide a refined capture of the actual inhalation exposure. Risk estimates and gender and age profiles are alarming, especially for young smokers. Application of toxicological approaches, combined with realistic assessment of the inhalation exposure levels, can support risk communication and management.


Assuntos
Cádmio/administração & dosagem , Simulação por Computador , Modelos Biológicos , Fumar Tabaco/efeitos adversos , Áustria , Humanos , Exposição por Inalação , Método de Monte Carlo , Medição de Risco , Fumantes , Fenômenos Toxicológicos
16.
Regul Toxicol Pharmacol ; 124: 104969, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34089813

RESUMO

Hexavalent chromium [Cr(VI)] exists in the ambient air at low concentrations (average upperbound ~0.1 ng/m3) yet airborne concentrations typically exceed EPA's Regional Screening Level for residential exposure (0.012 ng/m3) and other similar benchmarks, which assume a mutagenic mode of action (MOA) and use low-dose linear risk assessment models. We reviewed Cr(VI) inhalation unit risk estimates developed by researchers and regulatory agencies for environmental and occupational exposures and the underlying epidemiologic data, updated a previously published MOA analysis, and conducted dose-response modeling of rodent carcinogenicity data to evaluate the need for alternative exposure-response data and risk assessment approaches. Current research supports the role of non-mutagenic key events in the MOA, with growing evidence for epigenetic modifiers. Animal data show a weak carcinogenic response, even at cytotoxic exposures, and highlight the uncertainties associated with the current epidemiological data used in risk assessment. Points of departure from occupational and animal studies were used to determine margins of exposure (MOEs). MOEs range from 1.5 E+3 to 3.3 E+6 with a median of 5 E+5, indicating that current environmental exposures to Cr(VI) in ambient air should be considered of low concern. In this comprehensive review, the divergent results from default linear and MOE assessments support the need for more relevant and robust epidemiologic data, additional mechanistic studies, and refined risk assessment strategies.


Assuntos
Carcinógenos Ambientais/toxicidade , Cromo/toxicidade , Neoplasias Pulmonares/epidemiologia , Conjuntos de Dados como Assunto , Exposição Ambiental/efeitos adversos , Exposição Ambiental/normas , Epigênese Genética/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Exposição por Inalação/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/normas , Medição de Risco/métodos , Estados Unidos/epidemiologia , United States Environmental Protection Agency/normas
17.
Molecules ; 26(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809536

RESUMO

Pyrrolizidine alkaloids (PAs) are a class of natural toxins with hepatotoxicity, genotoxicity and carcinogenicity. They are endogenous and adulterated toxic components widely found in food and herbal products. In this study, a sensitive and efficient ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to detect the PAs in 386 kinds of Chinese herbal medicines recorded in the Chinese Pharmacopoeia (2020). The estimated daily intake (EDI) of 0.007 µg/kg body weight (bw)/day was adopted as the safety baseline. The margin of exposure (MOE) approach was applied to evaluate the chronic exposure risk for the genotoxic and carcinogenic potential of PAs. Results showed that PAs was detected in 271 out of 386 samples with a content of 0.1-25,567.4 µg/kg, and there were 20 samples with EDI values above the baseline, 0.007 µg/kg bw/day. Beyond that, the MOE values for 10 out of 271 positive samples were below 10,000. Considering the actual situation, Haber's rule was used to assume two weeks exposure every year during lifetime, and still the MOE values for four out of 271 positive samples were under 10,000, indicating these products may have potential health risk. The developed method was successfully applied to detect the PAs-containing Chinese herbal medicines. This study provides convincing data that can support risk management actions in China and a meaningful reference for the rational and safe use of Chinese herbal medicines.


Assuntos
Medicamentos de Ervas Chinesas/química , Alcaloides de Pirrolizidina/química , Carcinógenos/química , China , Cromatografia Líquida de Alta Pressão/métodos , Medicina Herbária/métodos , Humanos , Medição de Risco , Espectrometria de Massas em Tandem/métodos
18.
Environ Monit Assess ; 193(7): 443, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34169353

RESUMO

Four commonly consumed leafy vegetables, obtained from four major cities in southern Nigeria, were analysed for their polycyclic hydrocarbon (PAH) content using gas chromatography coupled with mass spectrometry (GC-MS). The estimated daily intake (EDI), margin of exposure (MOE), hazard index (HI) and total cancer risk (TCR); principal component analysis (PCA) and diagnostic ratios (DRs) were respectively used for risk evaluation and source identification of the detected PAHs. The results showed that the mean concentration (µg kg-1) of ∑16 PAHs in the vegetables ranged from 532 to 2261. The EDI values ranged from 459 to 4876, 1809 to 8378, 2733 to 13,036 and 4143 to 12,568 ng kg-1 bw day-1 for benzo[a]pyrene (BaP), PAH2, PAH4, and PAH8 for children exposure respectively, and from 115 to 1219, 452 to 2095, 683 to 3259 and 1036 to 3142 ng kg-1 bw day-1 for adult exposure respectively. The estimated MOE values were < 10,000, indicating that the vegetables were unsuitable for consumption. The HI values were < 1, suggesting that there were no potential non-carcinogenic risks, but the total cancer risk values (> 1 × 10-6) designated carcinogenic risk of PAHs with consumption of these vegetables. The DR and PCA result showed that PAHs originated from high-temperature pyrogenic processes and vehicular emissions.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Adulto , Criança , Cidades , Monitoramento Ambiental , Humanos , Nigéria , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Verduras
19.
Wei Sheng Yan Jiu ; 50(5): 832-836, 2021 Sep.
Artigo em Zh | MEDLINE | ID: mdl-34749880

RESUMO

OBJECTIVE: To investigate lead contamination in commercial foods in Guangzhou City, and to assess the health risk of dietary lead exposure in the residents. METHODS: Food samples were collected in 11 districts in Guangzhou City from 2017 to 2019.The samples were tested for lead by using inductively coupled plasma mass spectrometry. The dietary exposure to lead of residents of different age groups in Guangzhou was calculated in combination with the intake of foods from the food consumption survey of Guangzhou residents in 2011, and the margin of exposure(MOE) method was used to evaluate the health risk of the population. RESULTS: A todal of 3130 food samples of 15 categories were collected. The overall lead detection rate was 82.11%, the exceeding rate was 0.13%, and the average lead content was 0.031 mg/kg. The highest lead levels were found in bivalve, edible fungi and flour and flour products. Excessive levels of lead were found in bivalve, eggs and egg products, and flour and flour products. The average daily dietary intake of lead in people aged 3-6, 7-17, 18-59 and over 60 in Guangzhou were 0.368, 0.377, 0.326 and 0.337 µg/kg, respectively. Daily lead exposure of population with high consumption(P95) in various age groups through foods were 1.091, 1.079, 0.906 and 0.925 µg/kg, respectively. Brassica and leafy vegetables, rice and its products and meat were the main sources of dietary lead exposure, accounting for 53.28% of the total dietary lead exposure. The average MOE of lead in all age groups were greater than 1, but the P95 of MOE value of people aged 3-6 and 7-17 were 0.55 and 0.56, respectively, which presented certain health risks. CONCLUSION: There was a certain amount of lead exceeding the standard in commercial foods in Guangzhou. The average level of dietary lead exposure for residents of all ages posed a low risk to population health, but the dietary lead exposure risk of high-food consumers aged 3-6 and 7-17 posed certain health risks that deserve significant attention.


Assuntos
Contaminação de Alimentos , Chumbo , China , Exposição Dietética , Contaminação de Alimentos/análise , Humanos , Chumbo/análise , Medição de Risco , Verduras
20.
Rocz Panstw Zakl Hig ; 72(3): 253-265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34553879

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, they are also present in food, in which their presence results from environmental pollution and food processing processes. Many compounds from this group, such as benzo(a)pyrene show important toxicity, including genotoxic carcinogenicity. In food heavier PAHs significantly toxic are observed. OBJECTIVE: The aim of the study was assessment of consumers exposure to PAHs from the diet of surveyed respondents. The assessment of contaminants content in daily food rations is characterized by less uncertainty factor than the assessment based on data on the contamination of individual foodstuffs and their consumption by humans. MATERIAL AND METHODS: Research material consisted of daily diets obtained from respondents participating in the study. Content of 22 PAHs (fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo(c)fluorene, benz(a)anthracene, chrysene, 5-methylchrysene, perylene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(j)fluoranthene, benzo(e) pyrene, benzo(a)pyrene, benzo(ghi)perylene, indeno(1,2,3-cd)pyrene, dibenzo(a,h)anthracene, dibenzo(a,e)pyrene, dibenzo(a,l)pyrene, dibenzo(a,h)pyrene, dibenzo(a,i)pyrene) in each of diets was tested using liquid chromatography with a fluorescence detector. The samples were purified by saponification, size exclusion chromatography (SEC) and solid phase extraction (SPE). RESULTS: 52 respondents (n=52) took part in the study. The highest median of PAHs were found for pyrene (1.412 µg/kg), phenantrene (1.276 µg/kg), fluorene (1.151 µg/kg) and fluoranthene (1.087 µg/kg), they were about 10-80 higher than the levels of heavier PAHs. In group of heavy PAHs quantitatively prevailed benzo(e)pyrene (0.109 µg/kg), benzo(b) fluroanthene (0.070 µg/kg), benzo(ghi)perylene (0.065 µg/kg) and perylene (0.059 µg/kg). Generally the median level of contamination with light PAHs was 6.045 µg/kg, while with heavy ones 0.504 µg/kg, in the case of the sum of 4 PAHs regulated in EU law content was 0.301 µg/kg. In the tested samples average 24% of the PAH content was pyrene, light PAHs with a lower toxicity potential accounted for 92% of the content of tested compounds. Sum of 4 regulated PAHs accounted for 58% of content compounds selected by the EU as significant for the assessment of food contamination by PAHs. The composition of the participants' diets was analyzed in terms of determining factors influencing on high levels of PAHs. They were high fat level and presence of smoked or grilled meat and fish products. The mean exposure to benzo(a)pyrene was 0.52 ng/kg b.w. per day, while for the sum of 4 PAHs 3.29 ng/ kg b.w. per day. For light PAHs high exposure was 90.6 ng/kg b.w. per day, while for heavy PAH it was 10.7 ng/kg b.w. per day. Risk assessment was performed by calculating the value of margin of exposure (MoE), which for benzo(a)pyrene and for sum of 4 PAHs were above 25,000 in both considered: mean and high exposure scenario. CONCLUSIONS: Studied diets were a source of exposure to PAHs. Higher levels have been reported for light, less toxic PAH as compared to heavy PAH. In both considered scenarios margin of exposure were >25 000. In case of studied diets no risk for consumer was found.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Animais , Benzo(a)pireno/análise , Exposição Dietética , Contaminação de Alimentos/análise , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Medição de Risco
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